L-Glutamic acid is the main excitatory neurotransmitter in the mammalian central nervous system (CNS)[1]. L-Glutamic acid has two major types of receptors: ionotropic (NMDA-, AMPA-, and kainate-selective iGluRs)[2] and metabotropic glutamate receptors[3]. L-Glutamic acid induces excitotoxicity by activating the postsynaptic N-methyl-D-aspartate receptors, leading to neurodegenerative diseases[4].
In vitro, L-Glutamic acid (0.1μM) was found to induce differentiation of the cell line of HL-60 promyelocytic leukemia into granulocytes or neutrophils[5]. L-Glutamic acid (5mM; 24h) rapidly upregulated HIF1α in Raw 264.7 cells in a dose- and time-dependent manner, particularly under hypoxic conditions[6]. A high concentration of L-Glutamic acid (0, 0.3, 1 or 5mM; 48h or 72h) inhibited differentiation and fusion of mouse skeletal myoblasts C2C12, which are key processes in myogenesis[7].
In vivo, Low dose of L-Glutamic acid (400μM/kg; once every 24 hours; i.v.) attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice[4]. L-Glutamic acid (750mg/kg; 24h) can mitigate chlorpyrifos (CPF)-induced oxidative stress in rats[8].
References:
[1] Croce N, Bernardini S, Di Cecca S, et al. Hydrochloric acid alters the effect of L-glutamic acid on cell viability in human neuroblastoma cell cultures. J Neurosci Methods. 2013 Jul 15;217(1-2):26-30.
[2] Bowie D. The many faces of the AMPA-type ionotropic glutamate receptor. Neuropharmacology. 2022 May 1;208:108975.
[3] Brosnan JT, Brosnan ME. Glutamate: a truly functional amino acid. Amino Acids. 2013 Sep;45(3):413-8.
[4] Ramanathan M, Abdul KK, Justin A. Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice. Behav Pharmacol. 2016 Oct;27(7):615-22.
[5] Kostanian IA, Nurieva RI, Novolotskaia EV, et al. Izuchenie vliianiia L-glutaminovoĭ kisloty na retseptsiiu tsitokinov kletkami HL-60 [Effect of L-glutamic acid on the reception of cytokines by HL-60 cells]. Bioorg Khim. 1998 Jan;24(1):3-9. Russian. PMID: 9551194.
[6] Rigual MDM, Angulo-Aguado M, Zagorac S, et al. Macrophages harness hepatocyte glutamate to boost liver regeneration. Nature. 2025 May;641(8064):1005-1016.
[7] Ban H, Nobe K, Kobayashi S. Inhibitory effects of high extracellular L-glutamate concentrations on skeletal myogenesis. Sci Rep. 2025 May 19;15(1):17364.
[8] Salyha N, Salyha Y. Protective role of l-glutamic acid and l-cysteine in mitigation the chlorpyrifos-induced oxidative stress in rats. Environ Toxicol Pharmacol. 2018 Dec;64:155-163.
L-Glutamic acid是哺乳动物中枢神经系统(CNS)中的主要兴奋性神经递质[1]。L-Glutamic acid有两种主要类型的受体:离子型(NMDA-, AMPA- and kainate-selective iGluRs)[2]和代谢型谷氨酸受体[3]。L-Glutamic acid对突触后N-甲基-D-天冬氨酸受体的激动作用产生兴奋毒性,从而导致神经退行性病变[4]。
体外实验中,L-Glutamic acid(0.1μM)被发现可以诱导HL-60早幼粒细胞白血病细胞系分化为粒细胞或中性粒细胞[5]。L-Glutamic acid(5mM; 24小时)在低氧条件下,以剂量和时间依赖性方式迅速上调Raw 264.7细胞中的HIF1α[6]。高浓度的L-Glutamic acid(0, 0.3, 1或5mM; 48小时或72小时)抑制了小鼠骨骼肌成肌细胞C2C12的分化和融合,而这些过程是肌生成的关键步骤[7]。
体内实验中,低剂量的L-Glutamic acid(400μM/kg; 每24小时一次; 静脉注射)减轻了双侧颈总动脉闭塞小鼠的神经功能障碍和兴奋毒性[4]。L-Glutamic acid(750mg/kg; 24小时)可以减轻氯吡啶(CPF)诱导的大鼠氧化应激[8]。
















